切换导航

UNC2025

现货
Catalog No.
B8016
口服生物可利用的双重MER/FLT3抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,050.00
现货
5mg
¥ 1,050.00
现货
25mg
¥ 3,150.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

UNC2025 is a potent and orally bioavailable Mer/Flt3 dual inhibitor with the IC50 value of 0.8/0.74 nM for Mer/Flt3[1].

In vitro: In duplicate versus 305 kinases at Carna Biosciences using a microcapillary electrophoresis assay, UNC2025 inhibited Mer and Flt3 with the greatest potency. In B-ALL 697 cell lysates using the ATP ActivX probe assay, UNC2025 inhhibited the activity of Mer with an IC50 of 0.05 nM. In 697 B-ALL cells, UNC2025 potently inhibited Mer phosphorylation with an IC50 of 2.7 nM. Similarly, in Flt3-ITD positive Molm-14 acute myeloid leukemia cells, treatment with UNC2025 decreased phosphorylation of Flt3 with an IC50 of 14 nM. In soft agar cultures of the A549 NSCLC and Molm-14 AML cell lines, incubation withUNC2025 significantly inhibited colony formation, which was known to depend on Merand Flt3,respectively, for optimal expression of oncogenic phenotypes. Much higher concentrations of UNC2025 were required to effectively inhibit phosphorylation of Axl (IC50 = 122 nM) and Tyro3 (IC50 = 301 nM)[1].

In vivo: In mice with human leukemia xenografts, a single dose of UNC2025 (3 mg/kg) administered orally was sufficient to decrease Merphospho-protein levels in bone marrow leukemia cells by greater than 90% [1].

Reference:
[1]. Zhang W1,DeRyckere D,Hunter D,Liu J,Stashko MA,Minson KA, et,al. UNC2025, a potent and orally bioavailableMER/FLT3dual inhibitor.J Med Chem.2014 Aug 28;57(16):7031-41. doi: 10.1021/jm500749d. Epub 2014 Aug 6.

文献引用

1. McDaniel NK, Cummings CT, et al. "MERTK mediates intrinsic and adaptive resistance to AXL-targeting agents." Mol Cancer Ther. 2018 Aug 9. pii: molcanther.1239.2017. PMID:30093568

Chemical Properties

StorageDesiccate at -20°C
M.Wt476.66
Cas No.1429881-91-3
FormulaC28H40N6O
Solubility≥23.85mg/mL in DMSO
Chemical Name(1r,4r)-4-(2-(butylamino)-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexanol
SDFDownload SDF
Canonical SMILESCN1CCN(CC2=CC=C(C3=CN([C@@H]4CC[C@@H](O)CC4)C5=NC(NCCCC)=NC=C35)C=C2)CC1
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

697 B-ALL细胞; Flt3-ITD阳性Molm-14急性骨髓性白血病细胞; A549 NSCLC细胞

溶解方法

在DMSO中的溶解度>23.9mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0-300 nM; 1 h

应用

在697 B-ALL细胞中,UNC2025抑制Mer磷酸化,IC50为2.7nM。在Flt3-ITD阳性的Molm-14急性骨髓性白血病细胞中,UNC2025抑制Flt3的磷酸化,IC50为14nM。在A549 NSCLC细胞和Molm-14 AML细胞中,UNC2025以Mer依赖性和Flt3依赖性方式抑制集落形成。

动物实验[1]:

动物模型

携带人类白血病异种移植物的小鼠

剂量

3 mg/kg;口服

应用

在携带人类白血病异种移植物的小鼠中,UNC2025抑制骨髓白血病细胞中超过90%的Mer磷酸化水平。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Zhang W1,DeRyckere D,Hunter D,Liu J,Stashko MA,Minson KA, et,al. UNC2025, a potent and orally bioavailable MER/FLT3 dual inhibitor. J Med Chem.2014 Aug 28;57(16):7031-41. doi: 10.1021/jm500749d. Epub 2014 Aug 6.

质量控制

化学结构

UNC2025

相关生物数据

UNC2025